Hemangioma of the skin can occur on the eyelids, face, arms, legs, or any other parts of the body. It can not only be cosmetically disfiguring and psychologically disturbing, but can also cause functional disability, e.g., blindness, if it occurs on the places such as eyelids.
Current available treatments include corticosteroids (oral or injection), laser or surgery. Most recently, systemic use of propranolol was reported to successfully treat severe capillary hemangioma in infants. Most of these treatments are invasive and involve significant adverse effects, including severe ones such as scarring and/or discoloration of the skin, bleeding of surgical wounds, and respiratory or heart failures.
Capillary hemangioma is the most common benign tumor of the eyelid/orbit in children and affects up to 2% of infants, with a female to male ratio of 3:2. (Peralta, R. J. and Glavas, I. P., EyeNet, 2009, 35-37). Capillary hemangioma on the eyelids or face affects over 1.7 million children in USA and over 10 million children worldwide. If it is not treated promptly, it could cause irreversible blindness. The incidence of cutaneous hemangioma is much higher across all ages. Over millions of people can be affected. Cutaneous hemangioma can occur throughout human body and cause physically disfiguring and psychologically disturbing lesions in all age groups affected. It can also cause severe disabilities, such as blindness, in young children.
Systemic or intralesional corticosteroids are commonly used as first line treatment. Alternative treatments include laser photocoagulation, surgical excision and immunomodulators (cyclophosphamide and interferon alfa 2-a, usually reserved for life- or sight-threatening lesions due to their serious side effects).
Most of the treatments reported are associated with complications. Surgical excision is difficult due to the potential for hemorrhage. Immunomodulators have severe systemic adverse effects, for example, myelosuppression and hepatotoxicity for cyclophosphamide, and neurotoxicity (spastic displagia) for interferon alfa-2a.
Even the first-line treatments (i.e., oral or injectable corticosteroids) involve systemic complications. Side effects of systemic corticosteroids include increased risk of hypertension, adrenal cortical insufficiency, growth delay, immunosuppression, gastrointestinal bleeding, diabetes mellitus, weight gain, and behavioral changes. Intralesional corticosteroid injection can cause local complications, including dystrophic periocular calcifications, skin hypopigmentation, fat atrophy, eyelid necrosis (disfiguring), central retinal artery occlusion (sudden blindness), and adrenal suppression (growth retardation in children).
In addition to the side effects, all the currently available treatment options require significant time and effort of both physicians and patients. Clinical physicians have to initiate the treatments and monitor the patients very closely during therapy due to the possibility of severe systemic complications.
More recently, a systemic application of propranolol was reported to successfully treat severe hemangioma of infants. (Léauté-Labrèze, C. et al., New Engl. J. Med., 2008, 358:2649-2651). Significant shrinkage of the hemangioma occurred by about 24 hours after the initiation of systemic propranolol. Propranolol is a nonselective betal and beta2 adrenergic receptor blocker used to treat patients with heart diseases and hypertension. The mechanism by which propranolol reduces hemangioma is unclear. It is proposed that propranolol's beta2-mediated vasoconstrictive effect reduces expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) genes, which are the two crucial proangiogenic factors involved in the growth (involution) phase of hemangiomas. During the involution phase, both vascular endothelial and interstitial cells are actively dividing.
However, oral application of propranolol, as suggested by the study, can cause severe systemic complications, including bronchospasm, vasospasm, systemic lupus erythematosus, heart block, severe bradycardia, hypotension, and congestive heart failure. (Léauté-Labrèze, C. et al., New Engl. J. Med., 2008, 358:2649-2651). Thus, there remains a need for effective treatments that do not have severe or life-threatening side effects.